School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australia and Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Pde, Parkville, VIC 3052, Australia.
J Mater Chem B. 2020 Feb 26;8(8):1672-1681. doi: 10.1039/c9tb02586c.
Candida albicans (C. albicans) is a common fungal pathogen causing both localised and systemic infections. The majority of these infections are promoted by biofilm formation, providing a protective matrix for the embedded fungi thereby evading the host immune defence and promoting resistance against anti-mycotic agents. In this study, pH-responsive micellar systems based on poly-(ethylene glycol) ethyl ether methacrylate (PEGMA) and poly 2-(diethylamino) ethyl methacrylate (DEAEMA) block-copolymers of P(PEGMA-b-DEAEMA) were specifically developed and loaded with the antifungal itraconazole (ICZ) to defeat C. albicans biofilms. The P(PEGMA-b-DEAEMA) di-block polymer micelles demonstrated a particle size of 55 ± 6 nm and high ICZ loads (12.0 ± 0.5% w/w). Within the biofilm's acidic microenvironment, tertiary amines of the pH-sensitive DEAEMA block are protonated, altering their conformation and enhancing the release of the micellar contents. Encapsulation of ICZ within micelles significantly enhanced the activity against C. albicans biofilms, with a significant reduction in the biofilm biomass (>50%) and in the number of viable cells (2.4 Log reduction) achieved, compared with the non-encapsulated ICZ. Confocal microscopy revealed a high affinity and accumulation of the micelles in C. albicans biofilms as a result of their size and specific electrostatic interaction, hence their improved activity. P(PEGMA-b-DEAEMA) based pH-responsive micelles offer significant potential as antifungal carriers for controlling Candida infections.
白色念珠菌（C. albicans）是一种常见的真菌病原体，可引起局部和全身感染。这些感染大多数是由生物膜形成引起的，生物膜为嵌入的真菌提供了保护基质，从而逃避宿主免疫防御并促进对抗真菌药物的耐药性。在这项研究中，专门开发了基于聚（乙二醇）乙基醚甲基丙烯酸酯（PEGMA）和聚 2-（二乙基氨基）乙基甲基丙烯酸酯（DEAEMA）的 pH 响应胶束系统，并用抗真菌药物伊曲康唑（ICZ）负载以击败白色念珠菌生物膜。P(PEGMA-b-DEAEMA)两亲嵌段共聚物胶束的粒径为 55±6nm，负载量高（12.0±0.5%w/w）。在生物膜的酸性微环境中，pH 敏感的 DEAEMA 嵌段中的叔胺质子化，改变其构象并增强胶束内容物的释放。ICZ 包封在胶束中显著提高了对白色念珠菌生物膜的活性，与未包封的 ICZ 相比，生物膜生物量（>50%）和存活细胞数量（2.4Log 减少）显著降低。共聚焦显微镜显示，胶束由于其大小和特定的静电相互作用，对白色念珠菌生物膜具有高亲和力和积累，因此其活性得到提高。基于 P(PEGMA-b-DEAEMA)的 pH 响应胶束作为控制念珠菌感染的抗真菌载体具有很大的潜力。
